Peptide-based scaffolds for the culture and maintenance of primary human hepatocytes

We report here the use of a nanofibrous hydrogel as a 3D scaffold for the culture and maintenance of functional primary human hepatocytes. The system is based on the cooperative assembly of a fiber-forming peptide component, fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF), and the integrin-binding functional peptide ligand, Fmoc-arginine-glycine-aspartic acid (Fmoc-RGD) into a nanofibrous gel at physiological pH. This Fmoc-FF/RGD hydrogel was formulated to provide a biomimetic microenvironment with some critical features such as mechanical properties and nanofiber morphology, which were optimized to support hepatocyte culture. The material was shown to support maintenance and function of encapsulated primary human hepatocytes as indicated by actin staining, qRT-PCR, and functional cytochrome P450 assays. The designed gel was shown to outperform Matrigel in cytochrome P450 functional assays. The hydrogel may prove useful for liver development and disease models, as well as providing insights into the design of future implantable scaffolds for the regeneration of liver tissue in patients with liver disease.

Auxin and carotene biosynthesis by the bacterium Pantoea agglomerans

Monitoring of auxin and carotene during cultivation of the Pantoea agglomerans strain IB-BF revealed that the maximum yield of the target products is provided not by population density, but by the qualitative composition of the nutrient medium and the need for a larger peptide component of the substrate (rich amino acid set), which is part of the standard LB medium.

Impact of C-Terminal Chemistry on Self-Assembled Morphology of Guanosine Containing Nucleopeptides

Herein, we report the design and characterization of guanosine-containing self-assembling nucleopeptides that form nanosheets and nanofibers. Through spectroscopy and microscopy analysis, we propose that the peptide component of the nucleopeptide drives the assembly into β-sheet structures with hydrogen-bonded guanosine forming additional secondary structures cooperatively within the peptide framework. Interestingly, the distinct supramolecular morphologies are driven not by metal cation responsiveness common to guanine-based materials, but by the C-terminal peptide chemistry. This work highlights the structural diversity of self-assembling nucleopeptides and will help advance the development of applications for these supramolecular guanosine-containing nucleopeptides.

Analysis of peptide component of tissues under the condition of experimental obesity in rats

Obesity is characterized by a certain pathological imbalance in the mechanisms of proteolysis, which results in an increase in the number of degraded protein molecules, their fragments and the peptide pool in the tissues. Despite a significant number of literature on the biochemistry of obesity, the issue of the participation of proteolytic processes in the pathogenesis of obesity, their features and potential effects on metabolism is not well understood. At the same time, the appearance in the bloodstream of atypical protein molecules can be an important component of this pathology. Studying the processes of formation of these molecules can be very useful in planning strategies for correcting the development of this pathological condition, and the molecules described can be used as marker molecules for the development of obesity. The results of this work are the identification of changes in the quantitative and qualitative composition of the peptide component of the fraction of medium-weight molecules in rat tissues under experimental obesity. Chromatography, which separates by size, shows changes in the number of peaks and molecular weight of the peptide molecules in homogenates of obese rat tissue. The results indicate a certain imbalance in the proteolysis system with the development of obesity caused by the consumption of high-calorie diets, which in turn can be a potential cause of the appearance of certain non-physiological mechanisms in the functioning of metabolism in this pathology. This, in turn, can be triggers for the development of concomitant pathology and complicate the correction of the metabolic profile in the development of obesity. Further studies of the characteristics of changes in the peptide pool in rat tissues can contribute to a better understanding of biochemical processes in the context of this pathology, which is important for the development of approaches for the diagnosis and treatment of obesity. The study of potential mechanisms for the development of a dysfunction of the proteolysis system and methods for its correction can be successfully applied when working out strategies for treating various pathological conditions of the body, where a certain imbalance in the functioning of this system occurs.

Chemical and Biological Characteristics of Antimicrobial α-Helical Peptides Found in Solitary Wasp Venoms and Their Interactions with Model Membranes

Solitary wasps use their stinging venoms for paralyzing insect or spider prey and feeding them to their larvae. We have surveyed bioactive substances in solitary wasp venoms, and found antimicrobial peptides together with some other bioactive peptides. Eumenine mastoparan-AF (EMP-AF) was the first to be found from the venom of the solitary eumenine wasp Anterhynchium flavomarginatum micado, showing antimicrobial, histamine-releasing, and hemolytic activities, and adopting an α-helical secondary structure under appropriate conditions. Further survey of solitary wasp venom components revealed that eumenine wasp venoms contained such antimicrobial α-helical peptides as the major peptide component. This review summarizes the results obtained from the studies of these peptides in solitary wasp venoms and some analogs from the viewpoint of (1) chemical and biological characterization; (2) physicochemical properties and secondary structure; and (3) channel-like pore-forming properties.

Efficiency of inosine glycyl-cysteinyl-glutamate disodium and pyridoxine in acute poisoning by unsymmetrical dimethylhydrazine

Effectiveness of pyridoxine hydrochloride and inosine glycyl-cysteinyl-glutamate dinatrium (molixan) in monotherapy and in combination in acute poisoning by unsymmetrical dimethylhydrazine on survival, blood biochemical indicators and the state of plasma coagulation hemostasis was assessed. Unsymmetrical dimethylhydrazine was administered intraperitoneally at a dose of 115 mg/kg (LD50) once. Drugs under examination were also admistered intraperitoneally: pyridoxine hydrochloride in a dose of 50 mg/kg once, 30 minutes after the administration of unsymmetrical dimethylhydrazine, the inosine glycyl-cysteinyl-glutamatedinatrium (molixan) in a dose of 60 mg/kg seven times: 30 minutes after the administration of unsymmetrical dimethylhydrazine, and then daily for 6 days. Biochemical parameters of blood, plasma coagulation hemostasis, were evaluated 7 days after the administration of unsymmetrical dimethylhydrazine. The use of pyridoxine as a monotherapy and in combination with molixan prevents death of experimental animals and the development of convulsive syndrome. In addition, the combination of molixan with pyridoxine eliminates the development of toxic lesions of liver that is having hepatoprotective effect. The efficiency of molixan as hepatoprotector, apparently, related to the fact that in its structure it is a combined preparation containing the peptide and purine components. The peptide component (glycyl-cysteinyl-glutamate dinatrium) is a pharmacological analogue of oxidized glutathione, purine is represented by inosine. Oxidized glutathione has cytoprotective activity, inhibits the cytolysis of hepatocytes, and reduces the severity of inflammatory process during toxic damage of liver cells by the products of metabolism of xenobiotics. Inosine also has hepatoprotective properties. As a precursor to the synthesis of adenosine triphosphoric acid and nucleotides, it stimulates a number of metabolic processes in body, supports energy balance in various tissues, particularly in liver and myocardium.

A modular self-assembly approach to functionalised β-sheet peptide hydrogel biomaterials

Designed complementary peptides self-assembled into β-sheet fibrils under physiological conditions to give cell-compatible hydrogels. N-terminal modification of one peptide component with RGD improved fibroblast viability and attachment.